PROJECTSUMMARY/ABSTRACT This proposal addresses the compelling public health issue of the problem of childhood obesity in the Hispanic (Mexican-?American) population. In this context, one of the most striking epidemiological observations is that Hispanic immigrants in the U.S. exhibit a progressive and pronounced decline in health (obesity/ adiposity) over time and across generationsthatisevidentevenafteraccountingforsocioeconomicstatus.Theprevailingparadigminvokestheconstruct ofacculturation(post-?migrationacquisitionofhostcultureand/orlossofheritageculture)andpositsthishealthdecline isabiologicalconsequenceofsomeofacculturation?spsychosocialandbehavioralsequelae(increasingstress,declining social ties, adoption of unhealthy diet). However, research has overlooked one crucial point: a major feature of this phenomenon is its intergenerational component, and yet intergenerational transmission is unaddressed. Our proposal seeks to address this important limitation. We propose that the cause of the observed intergenerational escalation in obesity among Mexican-?Americans may, in part, originate during the intrauterine period of life. At this time, maternal acculturation-?related processes may impact fetal development to produce phenotypic alterations in the structure and function of cells, tissues and organ systems that increase susceptibility for obesity/adiposity (i.e., the concept of ?fetal/developmentalprogrammingofhealthanddiseaserisk?). We propose to conduct a prospective, longitudinal study in a representative cohort of N=300 first-? and second-? generation Mexican-?American mothers and their offspring from early gestation through birth till 6-?month age. We will conceptualize, operationalize and analyze acculturation as a multi-?dimensional construct. We will quantify child adiposity(%fatmass)atbirthandat6-?moagebydual-?energyX-?rayabsorptiometry(DXA)whole-?bodyimaging.Wewill address the following specific aims: Aim 1: Test the hypothesis that maternal acculturation is prospectively associated withnewbornandinfantbodycomposition(adiposity).Aim2:Testthehypothesisthatgestationalendocrine(cortisol, CRH), immune (IL-?6, TNF-??, CRP), oxidative (5-?iPF2?-?VI), and metabolic (glucose, insulin) biology across pregnancy mediatestheeffectofmaternalacculturationonnewbornandinfantbodycomposition(adiposity).Aim3:Identifyand quantifythepotentiallymodifiablematernalpsychological,behavioralandbiophysicalcharacteristicsthatareassociated withacculturationandmayaccountforitsimpactongestationalbiologyandchildbodycomposition(adiposity). Wehaveassembledaninterdisciplinaryteamofestablishedinvestigatorswithcomplementaryexpertise;performeda feasibility analysisdocumenting our ability torecruit and retainthe proposed study population andimplement all elements of the study protocol; and collected and present preliminary datain support of the key tenets of our proposal.OurstudywillgeneratenewinformationaboutthehealthofMexicanAmericans,shedmorelightonthecauses and mechanisms of intergenerational cycles of vulnerability, and provide a basis for developing specific translational targetsforfutureinterventionstudies.